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1.
Chem Biol Interact ; 394: 111003, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38608998

RESUMO

The use of flavored e-liquids in electronic nicotine delivery systems (ENDS) has become very popular in recent years, but effects of these products have not been well characterized outside the lung. In this study, acute exposure to the popular flavoring vanillin (VAN) was performed on human proximal tubule (HK-2) kidney cells. Cells were exposed to 0-1000 µM VAN for 24 or 48 h and cellular stress responses were determined. Mitochondrial viability using MTT assay showed a significant decrease between the control and 1000 µM group by 48 h. Seahorse XFp analysis showed significantly increased basal respiration, ATP production, and proton leak after 24 h exposure. By 48 h exposure, these parameters remained significantly increased in addition to non-mitochondrial respiration and maximal respiration. Glycolytic activity after 24 h exposure showed significant decreases in glycolysis, glycolytic capacity, glycolytic reserve, and non-glycolytic acidification. The autophagy markers microtubule-associated protein 1A/1B light chain 3 (LC3B-I and LC3B-II) were probed via western blotting. The ratio of LC3B-II/LC3B-I was significantly increased after 24 h exposure to VAN, but by 48 h this ratio significantly decreased. The mitophagy marker PINK1 showed an increasing trend at 24 h, and its downstream target Parkin was significantly increased between the control and 750 µM group only. Finally, the oxidative stress marker 4-HNE was significantly decreased after 48 h exposure to VAN. These results indicate that acute exposure to VAN in the kidney HK-2 model can induce energy and autophagic changes within the cell.


Assuntos
Autofagia , Benzaldeídos , Células Epiteliais , Aromatizantes , Túbulos Renais Proximais , Humanos , Autofagia/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Aromatizantes/farmacologia , Aromatizantes/toxicidade , Benzaldeídos/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Linhagem Celular , Glicólise/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Metabolismo Energético/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
2.
Drug Alcohol Depend ; 251: 110938, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37651811

RESUMO

BACKGROUND: Evidence for the effectiveness of menthol cigarette bans comes mostly from studies of adults that smoke. This experiment evaluated whether the absence of menthol products from a convenience store influenced young people's susceptibility to cigarette smoking after they shopped in the store. METHODS: This experiment took place in the RAND StoreLab (RSL), a life-sized research convenience store. A three-group, between-subjects design was used. Study conditions differed in the mix of flavored tobacco products the RSL displayed: 1) All tobacco-, sweet-, and menthol-flavors displayed; 2) only tobacco- and menthol-flavors displayed; and 3) only tobacco-flavors displayed. Participants were randomly assigned to shop in the RSL under one of these conditions and after shopping, completed measures of their susceptibility to cigarette smoking, one measure for menthol cigarettes and one for unflavored cigarettes (scores on each susceptibility measure was dichotomized: 0 = not susceptible; 1 = susceptible). RESULTS: Multivariable logistic regression assessed the main effects of condition on susceptibility to smoking menthol and unflavored cigarettes. There was no condition effect on susceptibility to smoking unflavored cigarettes. However, removing menthol-flavored products significantly increased participants' susceptibility to smoking menthol cigarettes compared to when all flavored products were available (OR = 3.66, 95% CI [1.33, 10.03]). This significant effect was only found among young people with some pre-existing risk of cigarette smoking (OR = 5.92, 95% CI [1.81, 19.39]). CONCLUSION: Results suggest the need to consider that menthol bans could unintentionally increase the appeal of menthol cigarettes among youth already at risk of smoking.


Assuntos
Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Adulto , Adolescente , Humanos , Mentol , Aromatizantes/farmacologia , Comércio
3.
Exp Clin Psychopharmacol ; 31(4): 817-828, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36656717

RESUMO

The U.S. Food and Drug Administration proposed new product standards that would ban characterizing flavors (other than tobacco) in cigars. To inform this regulatory action, we compared physiological effects, use behavior, and subjective effects of four popular cigar flavors in cigar-naïve young adult cigarette smokers. Across five laboratory visits, participants (n = 25) used and evaluated own brand (OB) cigarettes or Black & Mild cigars (original, wine, apple, and cream flavors). Linear mixed models tested differences in saliva nicotine, exhaled carbon monoxide (CO), heart rate (HR), blood pressure (BP), puff topography, and subjective effects (p < .05). Compared to all cigars, OB resulted in higher nicotine boost (953 vs. < 300 ng/ml) and lower CO boost (4 vs. 8-9 ppm). Nicotine boost for original cigars (283 ng/ml) was significantly higher than wine (190 ng/ml). All products significantly increased HR/BP relative to baseline, but across time wine and apple cigars were associated with significantly lower HR than OB and BP effects varied. Relative to OB, participants took approximately 0.5 s longer puffs for all cigars and took significantly larger puffs (+ 21%-24%) of original, wine, and apple cigars. OB was rated more positively than all cigars, which had similar subjective effects. Wine cigars were disliked most and were less effective in reducing tobacco abstinence symptoms than OB; cream cigars were harsher and had stronger flavor intensity than original. The consistency in toxicant exposure, use behavior, and subjective effects across cigar flavors, including original, highlights the need for product standards to interpret characterizing flavors subject to prohibition broadly. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Nicotina , Produtos do Tabaco , Humanos , Adulto Jovem , Nicotina/farmacologia , Fumantes , Aromatizantes/farmacologia , Frequência Cardíaca
4.
Swiss Med Wkly ; 154: 3733, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38579318

RESUMO

AIMS: To explore the effects of prices and flavour availability on the appeal of different tobacco and nicotine products, including conventional cigarettes, Electronic Nicotine Delivery Systems (ENDS) and Heated Tobacco Systems (HTS) among an adult population in Switzerland. METHODS: We performed a Discrete Choice Experiment among a group of Swiss aged ≥18 years via the online recruiting platform Prolific in a convenience sample. Our sample included both non-smokers and smokers. We used a within-subject, alternative-specific block design in a series of choice sets including different smoking products. We fixed the attributes of nicotine content (high or medium) and harmfulness (in years of life lost) for each product. Attributes of interest included price (ranging from CHF 5 to 25 in increments of 5) and flavour (fruity/menthol vs none/tobacco flavour). We performed a conditional logistic regression on the attributes' influence on the appeal of cigarettes, ENDS and HTS. RESULTS: A total of 108 out of 153 participants (n = 25 smokers and n = 83 non-smokers, completion rate = 71%) successfully completed our pilot survey experiment. We found that, in general, increasing the price of combustible cigarettes, ENDS and HTS by one standard deviation (around CHF 7) reduced their appeal by approximately 66% (relative risk [RR]: 0.34; 95% CI: 0.28-0.42). Unflavoured alternative nicotine products were found to be less appealing than flavoured products, especially for non-smokers, with a 86% decrease in appeal (RR: 0.14; 95% CI: 0.13-0.16). For non-smokers, an increase in price by one standard deviation was associated with a decrease in the appeal of any product by approximately 19% (RR: 0.81; 95% CI: 0.72-0.92). For smokers, the effect sizes were smaller, but overall, the appeal of all products decreased with increasing prices and reduced flavours. CONCLUSIONS: Our Discrete Choice Experiment suggests that, for the Swiss context, limiting the availability of flavours for alternative smoking products has the potential to reduce their appeal to non-smokers by 86% and that a small but significant increase in prices to CHF 15 for cigarettes, ENDS and HTS could lead to a major (around 66%) decrease in their appeal.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Adulto Jovem , Adolescente , Adulto , Nicotina/farmacologia , Projetos Piloto , Suíça , Fumar , Aromatizantes/farmacologia
5.
Drug Alcohol Depend ; 241: 109685, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36370533

RESUMO

BACKGROUND: The continued use of flavors in tobacco products has been a prominent factor in their popularity, yet little is known regarding their role in nicotine dependence. This study aimed to investigate the impact of tobacco flavoring on oral nicotine consumption in mice using the two-bottle choice (2BC) test and assessed the potential impact of age and sex in their interactions. METHODS: Adolescent and adult male and female C57BL/6J mice were used. First, voluntary consumption of tobacco flavor concentrate from a commercial electronic cigarette liquid vendor (Avail Vapor LLC) was measured; then, the effects of tobacco flavoring in combination with nicotine were examined. In one approach, tobacco flavor concentration was kept constant while nicotine concentration varied, and in the second, nicotine was kept constant while the tobacco flavor concentration varied. RESULTS: Overall, tobacco flavoring decreased oral nicotine consumption in mice, and its effects were sex- and age-dependent. Although females consumed the tobacco-flavored solution at a slightly higher rate than males, male mice were more sensitive to the effects of the combination (nicotine + tobacco). Furthermore, adolescent mice showed a starker reduction in nicotine consumption in the presence of tobacco flavoring compared to adult mice. This attenuation was most likely due to a basal aversion to the tobacco flavoring itself, thus, creating a negative synergistic effect with nicotine. CONCLUSIONS: Tobacco flavoring increases aversion to nicotine in the 2BC test in C57BL6J mice, suggesting that some flavors may diminish rather than enhance oral nicotine consumption in rodents.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Masculino , Feminino , Camundongos , Animais , Nicotina/farmacologia , Nicotiana , Aromatizantes/farmacologia , Camundongos Endogâmicos C57BL
6.
Molecules ; 27(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36234689

RESUMO

D-limonene (4-isopropenyl-1-methylcyclohexene) is an important compound in several citrus essential oils (such as orange, lemon, tangerine, lime, and grapefruit). It has been used as a flavoring agent and as a food preservative agent, with generally recognized as safe (GRAS) status. D-limonene has been well-studied for its anti-inflammatory, antioxidant, anti-cancer, and antibacterial properties. The antibacterial activity of D-limonene against food-borne pathogens was investigated in this study by preparing a D-limonene nanoemulsion. The D-limonene solution and nanoemulsion have been prepared in six concentrations, 0.04%, 0.08%, 0.1%, 0.2%, 0.4%, and 0.8% (v/v), respectively, and the antibacterial activity was tested against four food-borne pathogens (Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica, and Escherichia coli). The results showed that the D-limonene nanoemulsion had good nanoscale and overall particle size uniformity, and its particle size was about 3~5 nm. It has been found that the D-limonene solution and nanoemulsion have a minimal inhibitory concentration of 0.336 mg/mL, and that they could inhibit the growth of microorganisms efficiently. The data indicate that the D-limonene nanoemulsion has more antibacterial ability against microorganisms than the D-limonene essential oil. After bananas are treated with 1.0% and 1.5% D-limonene nanoemulsion coatings, the water loss of the bananas during storage and the percentage of weight loss are reduced, which can inhibit the activity of pectinase. The application of a biocoating provides a good degree of antibacterial activity and air and moisture barrier properties, which help with extending the shelf life of bananas.


Assuntos
Citrus , Filmes Comestíveis , Musa , Óleos Voláteis , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Cicloexenos/farmacologia , Escherichia coli , Aromatizantes/farmacologia , Conservantes de Alimentos/farmacologia , Limoneno/farmacologia , Óleos Voláteis/farmacologia , Poligalacturonase , Terpenos/farmacologia , Água/farmacologia
7.
Pak J Biol Sci ; 25(9): 803-815, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36098082

RESUMO

<b>Background and Objective:</b> Beetroot juice is a biological antioxidant and acts as health-promoting minerals as well as soluble fibres and vitamins. This study aimed to encapsulate the Beetroot Juice Powder (BJP) by the conjugate sodium caseinate (NaCas) and Maltodextrin (MD) to protect it from environmental conditions. Produced flavoured acid beverage using BJP encapsulated using conjugates. <b>Materials and Methods:</b> Nano-encapsulation of BJP (20, 30, 40 mg g<sup></sup><sup>1</sup>) and determine the encapsulation efficiency, size and zeta potential. Rats were divided into 4 groups as follows, negative control, positive control and 2 test groups that received free BJP or encapsulated BJP. All rats except the negative control group were injected with CCl<sub>4</sub> twice a week. <b>Results:</b> The NaCas-MD conjugate has the advantage over the NaCas-MD complex of higher stability and BJP binding, also showing high encapsulation efficiency (>93.75%) of different levels of BJP. The flavoured beverage from the addition of BJP encapsulated by conjugate has better sensory and technological properties than fortified with BJP in the complex. Injection with CCl<sub>4</sub> leads to a decrease in body weight, serum parameters including, protein, albumin, GSH, CAT and SOD, also increase ALT, AST, ALP and liver weight. Moreover, a variable pathological alteration in liver tissue was found. At the end of the experiment receiving encapsulated beetroot juice led to improvement in all above body and liver weight, all biochemical parameters and histopathological elevation. <b>Conclusion:</b> Thus, it could be concluded that flavoured beverage containing BJP encapsulated by conjugate is of acceptable quality and high antioxidant activity. Also, it has a remarkable protective effect against acute hepatotoxicity.


Assuntos
Antioxidantes , Substâncias Protetoras , Animais , Antioxidantes/metabolismo , Bebidas , Aromatizantes/farmacologia , Fígado , Substâncias Protetoras/farmacologia , Ratos , Verduras
8.
Food Chem Toxicol ; 168: 113365, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35970270

RESUMO

2-Methylfuran (2-MF) exists naturally in foods and is used as a flavoring agent. Furan, the core structure of 2-MF, possesses hepatocarcinogenicity in rodents. Accumulation of toxicological information on furan derivatives is needed to elucidate their carcinogenic mode of action. In the current study, we examined the comprehensive toxicological studies of 2-MF using gpt delta rats. 2-MF was intragastrically administered to groups of 10 male and 10 female Sprague-Dawley gpt delta rats at a dose of 0, 1.2, 6, or 30 mg/kg/day for 13 weeks. Effects of 2-MF on the hepatobiliary system including an increase in serum alkaline phosphatase were observed in the 6 and 30 mg/kg groups, and cholangiofibrosis was found in the 30 mg/kg group. The no observed adverse effect level was set at 1.2 mg/kg/day for both sexes and 1.14 mg/kg/day was determined as the benchmark dose low. The acceptable daily intake was calculated to be 11.4 µg/kg/day. Increases in the number and areas of glutathione S-transferase placental form-positive foci in the 30 mg/kg group were apparent, suggesting the hepatocarcinogenicity of 2-MF in rats. By contrast, the lack of increase in in vivo mutagenicity in the liver implied that 2-MF hepatocarcinogenesis may not involve genotoxic mechanisms.


Assuntos
Fosfatase Alcalina , Aromatizantes , Animais , Carcinógenos/toxicidade , Dano ao DNA , Relação Dose-Resposta a Droga , Feminino , Aromatizantes/farmacologia , Furanos/toxicidade , Glutationa Transferase , Fígado , Masculino , Testes de Mutagenicidade , Placenta , Gravidez , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Ratos Transgênicos
9.
Food Res Int ; 157: 111287, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35761595

RESUMO

Health concerns related to the intake of salt have encouraged the investigation into sodium reduction by examining the taste-taste interaction between the perception of saltiness and umami. The effect of saltiness enhancement and sodium reduction of four kinds of umami carrier (WSA, MSG, IMP, and I + G) in a salt model solution with different salt concentrations (2.03-13.94 g/L) were investigated using the two-alternative forced-choice (2-AFC) and generalized Labeled Magnitude Scale (gLMS). The saltiness difference thresholds (DT) under different umami carrier were further explored using the constant stimuli method. The results showed that umami carriers had effective effects of saliness enhancement in the salt solutions with different concentrations, and higher enhancemen levels were obtained at larger salt concentrations. The level of saltiness enhancement were varied between the different umami intensity and carriers, and WSA carrier with moderate intensity had the maximum sodium reduction percentages which reached to 24.25%. Besides, the DT values of saltiness taste were increased under umami carrier, which means that more salt can be reduced without evoking a variation in saltiness. The present work not only provided insight into the effect of umami chemicals on the saltiness perception and saltiness DT values but also presented valuable information regarding flavor when developing low sodium foods and contributing to the development of more healthful products that meet current nutritional recommendations.


Assuntos
Aromatizantes , Paladar , Aromatizantes/farmacologia , Compostos Orgânicos , Percepção , Sensação , Sódio , Cloreto de Sódio/farmacologia , Cloreto de Sódio na Dieta
10.
Dev Biol ; 481: 14-29, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34543654

RESUMO

Environmental teratogens such as smoking are known risk factors for developmental disorders such as cleft palate. While smoking rates have declined, a new type of smoking, called vaping is on the rise. Vaping is the use of e-cigarettes to vaporize and inhale an e-liquid containing nicotine and food-like flavors. There is the potential that, like smoking, vaping could also pose a danger to the developing human. Rather than waiting for epidemiological and mammalian studies, we have turned to an aquatic developmental model, Xenopus laevis, to more quickly assess whether e-liquids contain teratogens that could lead to craniofacial malformations. Xenopus, like zebrafish, has the benefit of being a well-established developmental model and has also been effective in predicting whether a chemical could be a teratogen. We have determined that embryonic exposure to dessert flavored e-liquids can cause craniofacial abnormalities, including an orofacial cleft in Xenopus. To better understand the underlying mechanisms contributing to these defects, transcriptomic analysis of the facial tissues of embryos exposed to a representative dessert flavored e-liquid vapor extract was performed. Analysis of differentially expressed genes in these embryos revealed several genes associated with retinoic acid metabolism or the signaling pathway. Consistently, retinoic acid receptor inhibition phenocopied the craniofacial defects as those embryos exposed to the vapor extract of the e-liquid. Such malformations also correlated with a group of common differentially expressed genes, two of which are associated with midface birth defects in humans. Further, e-liquid exposure sensitized embryos to forming craniofacial malformations when they already had depressed retinoic acid signaling. Moreover, 13-cis-retinoic acid treatment could significantly reduce the e-liquid induced malformation in the midface. Such results suggest the possibility of an interaction between retinoic acid signaling and e-liquid exposure. One of the most popular and concentrated flavoring chemicals in dessert flavored e-liquids is vanillin. Xenopus embryos exposed to this chemical closely resembled embryos exposed to dessert-like e-liquids and a retinoic acid receptor antagonist. In summary, we determined that e-liquid chemicals, in particular vanillin, can cause craniofacial defects potentially by dysregulating retinoic acid signaling. This work warrants the evaluation of vanillin and other such flavoring additives in e-liquids on mammalian development.


Assuntos
Benzaldeídos/administração & dosagem , Anormalidades Craniofaciais , Embrião não Mamífero/embriologia , Aromatizantes/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Produtos do Tabaco/toxicidade , Tretinoína/metabolismo , Animais , Benzaldeídos/farmacologia , Anormalidades Craniofaciais/induzido quimicamente , Anormalidades Craniofaciais/embriologia , Embrião não Mamífero/patologia , Aromatizantes/farmacologia , Xenopus laevis
11.
Nutrients ; 13(6)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070818

RESUMO

The short- and long-term consumption of monosodium glutamate (MSG) increases urinary pH but the effects on the metabolic pathways in the liver, kidney and the gut microbiota remain unknown. To address this issue, we investigated adult male Wistar rats allocated to receive drinking water with or without 1 g% MSG for 2 weeks (n = 10, each). We performed a Nuclear Magnetic Resonance (NMR) spectroscopy-based metabolomic study of the jejunum, liver, and kidneys, while faecal samples were collected for bacterial DNA extraction to investigate the gut microbiota using 16S rRNA gene sequencing. We observed significant changes in the liver of MSG-treated rats compared to controls in the levels of glucose, pyridoxine, leucine, isoleucine, valine, alanine, kynurenate, and nicotinamide. Among kidney metabolites, the level of trimethylamine (TMA) was increased, and pyridoxine was decreased after MSG-treatment. Sequencing of the 16S rRNA gene revealed that MSG-treated rats had increased Firmicutes, the gut bacteria associated with TMA metabolism, along with decreased Bifidobacterium species. Our data support the impact of MSG consumption on liver and kidney metabolism. Based on the gut microbiome changes, we speculate that TMA and its metabolites such as trimethylamine-N-oxide (TMAO) may be mediators of the effects of MSG on the kidney health.


Assuntos
Aromatizantes/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Rim/microbiologia , Fígado/microbiologia , Glutamato de Sódio/farmacologia , Animais , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Modelos Animais , Ratos , Ratos Wistar
12.
Mech Ageing Dev ; 198: 111518, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34139214

RESUMO

INTRODUCTION: Aging represents a major risk factors for metabolic diseases, such as diabetes, obesity, or neurodegeneration. Polyphenols and their metabolites, especially simple phenolic acids, gained growing attention as a preventive strategy against age-related, non-communicable diseases, due to their hormetic potential. Using Caenorhabditis elegans (C. elegans) we investigate the effect of protocatechuic, gallic, and vanillic acid on mitochondrial function, health parameters, and the induction of potential hormetic pathways. METHODS: Lifespan, heat-stress resistance and chemotaxis of C. elegans strain P X 627, a specific model for aging, were assessed in 2-day and 10-day old nematodes. Mitochondrial membrane potential (ΔΨm) and ATP generation were measured. mRNA expression levels of longevity and energy metabolism-related genes were determined using qRT-PCR. RESULTS: All phenolic acids were able to significantly increase the nematodes lifespan, heat-stress resistance and chemotaxis at micromolar concentrations. While ΔΨm was only affected by age, vanillic acid (VA) significantly decreased ATP concentrations in aged nematodes. Longevity pathways, were activated by all phenolic acids, while VA also induced glycolytic activity and response to cold. CONCLUSION: While life- and health span parameters are positively affected by the investigated phenolic acids, the concentrations applied were unable to affect mitochondrial performance. Therefore we suggest a hormetic mode of action, especially by activation of the sirtuin-pathway.


Assuntos
Envelhecimento , Ácido Gálico/farmacologia , Hormese , Hidroxibenzoatos/farmacologia , Polifenóis/farmacologia , Ácido Vanílico/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Anticarcinógenos/farmacologia , Caenorhabditis elegans , Quimiotaxia/efeitos dos fármacos , Quimiotaxia/fisiologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Aromatizantes/farmacologia , Resposta ao Choque Térmico/efeitos dos fármacos , Hormese/efeitos dos fármacos , Hormese/fisiologia , Longevidade/efeitos dos fármacos , Longevidade/genética , Redes e Vias Metabólicas/efeitos dos fármacos , Renovação Mitocondrial/efeitos dos fármacos , Renovação Mitocondrial/fisiologia
13.
Pharmacol Biochem Behav ; 206: 173207, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34019915

RESUMO

Electronic-cigarette's (ECIGs) popularity has grown over the last decade and changed the way individuals administer nicotine. Preclinical research is imperative for understanding the addictive properties and health-risks associated with ECIG use; however, there is not a standard dosing regimen used across research laboratories. The main objective was to determine how vapor puff durations, administration session length, and flavored e-liquid alter general and mood-disorder related behaviors while providing a foundation of vapor administration parameters. Adult male and female C57BL/6 mice were exposed to several nicotine-free unflavored vapor puff durations (1, 3, 6, or 10 s) and vapor administration session lengths (10 and 30 min) then measured on the following assays: locomotor activity (LMA), tail suspension test (TST), and light-dark test. The effects of mecamylamine and the time-course of vapor-induced depression of LMA also were assessed. Additionally, mice were exposed to flavored (strawberry and adventurers tobacco blend) vapor inhalation and measured on locomotor activity, tail suspension test, and light-dark test. Following both 10 and 30 min vapor administration session, there was a puff duration-dependent decrease in distance traveled, time in center, and rearing. The vapor-induced depression of LMA was not mediated by nicotine or nicotinic acetylcholine receptor (nAChR) activation and lasted 60-90 min. The 10 s puff duration produced an anxiogenic-like effect in the light-dark test by decreasing the time spent in the light side. Vapor inhalation did not significantly alter TST behavior. No significant effects of sex or flavor were found. The anxiogenic-like effects of nicotine-free vapor inhalation are concerning as many adolescents vape nicotine-free flavored e-liquid, and there is an association between ECIGs and mood disorders. Additionally, these studies demonstrate that vapor puff duration, but not vapor administration session length, is an important variable to consider during research design as it can become a confounding variable and alter baseline behaviors.


Assuntos
Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Vapor do Cigarro Eletrônico/farmacologia , Sistemas Eletrônicos de Liberação de Nicotina , Vaping/efeitos adversos , Administração por Inalação , Adolescente , Animais , Ansiedade/psicologia , Feminino , Aromatizantes/farmacologia , Humanos , Locomoção/efeitos dos fármacos , Masculino , Mecamilamina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Nicotina/farmacologia , Antagonistas Nicotínicos/farmacologia , Receptores Nicotínicos/metabolismo , Fatores Sexuais , Fatores de Tempo
14.
Neurobiol Dis ; 153: 105318, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33636386

RESUMO

Huntington's disease (HD) is a neurodegenerative disorder characterized by accumulation of mutant huntingtin protein and significant loss of neurons in striatum and cortex. Along with motor difficulties, the HD patients also manifest anxiety and loss of cognition. Unfortunately, the clinically approved drugs only offer symptomatic relief and are not free from side effects. This study underlines the importance of glyceryl tribenzoate (GTB), an FDA-approved food flavoring ingredient, in alleviating HD pathology in transgenic N171-82Q mouse model. Oral administration of GTB significantly reduced mutant huntingtin level in striatum, motor cortex as well as hippocampus and increased the integrity of viable neurons. Furthermore, we found the presence of sodium benzoate (NaB), a FDA-approved drug for urea cycle disorders and glycine encephalopathy, in the brain of GTB-fed HD mice. Accordingly, NaB administration also markedly decreased huntingtin level in striatum and cortex. Glial activation is found to coincide with neuronal death in affected regions of HD brains. Interestingly, both GTB and NaB treatment suppressed activation of glial cells and inflammation in the brain. Finally, neuroprotective effect of GTB and NaB resulted in improved motor performance of HD mice. Collectively, these results suggest that GTB and NaB may be repurposed for HD.


Assuntos
Benzoatos/administração & dosagem , Aromatizantes/farmacologia , Conservantes de Alimentos/farmacologia , Proteína Huntingtina/efeitos dos fármacos , Doença de Huntington/metabolismo , Córtex Motor/efeitos dos fármacos , Neostriado/efeitos dos fármacos , Benzoato de Sódio/farmacologia , Administração Oral , Animais , Benzoatos/farmacologia , Ácido Benzoico/farmacologia , Análise da Marcha , Força da Mão , Humanos , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Doença de Huntington/genética , Doença de Huntington/fisiopatologia , Camundongos , Camundongos Transgênicos , Córtex Motor/metabolismo , Neostriado/metabolismo , Teste de Campo Aberto , Teste de Desempenho do Rota-Rod , Benzoato de Sódio/metabolismo
15.
J Biomater Appl ; 36(4): 592-604, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33593129

RESUMO

The preferred cancer treatment is to achieve a high therapeutic effect as well as reduce side effects. In this study, we developed carrier-free nano drugs based on 5-fluorouracil (5FU) and cinnamaldehyde (CA) to meet the above goals. Two model drugs were spliced by acetal linkage and ester bond, which could self-assemble into nano drug particles (5FU-CA NPs) with a size of ∼170 nm. In vitro cell experiments showed 5FU-CA NPs were efficiently internalized by HepG2 cells. They then quickly exerted dual drug activities by the cleavage of acetal and ester bond, resulting in enhanced cell-killing efficacy and apoptosis. Synergistic mechanisms were achieved via the anti-metabolic effects mediated by 5FU-COOH and the oxidative damage induced by CA. In vivo anti-tumor evaluation further indicated that 5FU-CA NPs had higher tumor growth inhibition than 5FU-COOH/CA mixture (5FU-COOH + CA) and exhibited lower systemic toxicity under the same reducing dose of each drug. Overall, this is a successful synergistic anti-tumor attempt through rational self-assembly of drugs with different mechanisms and it can be extrapolated to other agents.


Assuntos
Antimutagênicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos/farmacologia , Aromatizantes/farmacologia , Fluoruracila/farmacologia , Nanopartículas/química , Acroleína/análogos & derivados , Animais , Antimutagênicos/química , Antineoplásicos/química , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Aromatizantes/química , Fluoruracila/química , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR
16.
J Food Sci ; 86(3): 1022-1032, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33615480

RESUMO

The effect of the flavor enhancers monoammonium glutamate (MAG), monosodium glutamate (MSG), disodium guanylate (GMP), and disodium inosinate (IMP) on intensifying salty taste in food matrices (shoestring potatoes, requeijão cheese, and beef burgers) with a reduction in the amount of sodium chloride (NaCl) present was evaluated. Experiments were conducted using a central composite rotational design with two variables: the concentrations of flavor enhancer and NaCl added in the food matrix. The effect of IMP was not significant (P > 0.05) on the intensity of salty taste in any of the matrices analyzed. GMP presented lower performance compared to MAG and MSG in intensifying the salty taste of the treatments, regardless of the reduction of NaCl. Compared to MSG and GMP, MAG showed greater efficiency in intensifying the salty taste in requeijão cheese and beef burger with a reduction of 25%, 50%, 75%, and 100% of NaCl. MSG presented higher efficiency compared to MAG and GMP when applied in shoestring potatoes for all reductions of NaCl tested (25%, 50%, and 75%). The ability of flavor enhancers to improve the salty taste depends on the effect of the flavor enhancer, the complexity of the food matrix, and the reduction of NaCl in foods. PRACTICAL APPLICATIONS: The complexity of the food matrix plays a significant role in the perception of salty taste in sodium-reduced products. In these products, sodium reduction may affect the taste enhancer's effect of enhancing salty taste. Therefore, this study broadens the knowledge of the effects of flavor enhancers on different foods, as well as the ability to enhance salty taste in food matrices with NaCl reduction. Moreover, it provides information on how to reduce the sodium content in these matrices while maintaining the same perception of salty taste as a conventional matrix.


Assuntos
Queijo/análise , Aromatizantes/farmacologia , Produtos da Carne/análise , Cloreto de Sódio na Dieta/análise , Solanum tuberosum/química , Paladar/efeitos dos fármacos , Animais , Bovinos , Humanos , Cloreto de Sódio na Dieta/metabolismo , Glutamato de Sódio/farmacologia , Solanum tuberosum/efeitos dos fármacos , Solanum tuberosum/metabolismo
17.
Food Chem ; 338: 128018, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32932086

RESUMO

The umami-enhancing effect of typical kokumi-active γ-glutamyl peptides was verified by sensory evaluation. To investigate the umami-enhancing molecular mechanism of the peptide on monosodium glutamate (MSG) taste, a novel hypothetical receptor, taste type 1 receptor 3 (T1R3)-MSG complex, was constructed. These peptides demonstrated strong interactions with T1R3-MSG. Moreover, four amino acid residues, Glu-301, Ala-302, Thr-305, and Ser-306, were critical in ligand-receptor interactions. In detail, γ-Glu-γ-Glu-Val (γ-E-γ-EV) readily interacts with T1R3 through hydrogen bonds and hydrophobic interactions. While γ-E-γ-EV did not bind to MSG, γ-Glu-Val (γ-EV) and γ-Glu-Leu (γ-EL) showed high binding affinity to MSG and interacted with T1R3 through hydrophobic bonds suggesting that the interactions between dipeptides and T1R3-MSG were weaker than tripeptides. These results demonstrated that kokumi-active γ-glutamyl peptides could enhance the umami taste of MSG, and exhibit synergistic effects in activating T1R3. This study provides a theoretical reference for interactions between the novel umami-enhancing substances and umami receptor.


Assuntos
Dipeptídeos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Glutamato de Sódio/metabolismo , Paladar , Adulto , Aminoácidos/química , Aminoácidos/metabolismo , Dipeptídeos/química , Feminino , Aromatizantes/química , Aromatizantes/farmacologia , Humanos , Ligação de Hidrogênio , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Simulação de Acoplamento Molecular , Receptores Acoplados a Proteínas G/química , Glutamato de Sódio/química , Glutamato de Sódio/farmacologia , Paladar/efeitos dos fármacos
18.
Exp Clin Psychopharmacol ; 29(6): 615-624, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32463279

RESUMO

Menthol is the only available flavor in combusted tobacco cigarettes; however, e-cigarettes are available in thousands of flavors. Research on flavors and rewarding properties of nicotine is limited. The present study sought to examine the acute rewarding effects of flavors inhaled from an e-cigarette, in combination with intravenous (IV) nicotine among cigarette smokers. In the present study, 24 menthol-preferring young adult (aged 18 to 30) cigarette smokers were tested under 3 different e-cigarette flavor conditions (menthol, green apple, or menthol + green apple) in a within-subject cross-over design. During each test session, each participant received 3 IV infusions (saline, 0.25 mg/70 kg nicotine, 0.5 mg/70 kg nicotine) administered 1 hr apart. The main outcome measures assessed cardiovascular, subjective, and cognitive domains. Compared with green apple or green apple + menthol, menthol produced higher ratings of "cooling" (ps < 0.01). Craving was rated higher following administration of green apple and the combined menthol + apple flavor compared to menthol alone (ps < 0.05). As expected, IV-nicotine dose-dependently increased the ratings of subjective liking/disliking and peak heart rate, improved cognitive performance, and reduced smoking urges (all ps < 0.05). These subjective, cognitive, and physiological effects of nicotine were not affected by any flavor condition. The present findings did not support an interaction between IV-nicotine dose and inhaled flavor for acute effects of nicotine. Green apple flavor, alone or in combination with menthol, could result in higher craving or insufficiently alleviate craving, relative to menthol flavor alone. Additional research is warranted to examine extended exposure to inhaled flavors on the rewarding and addictive effects of nicotine. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Aromatizantes/farmacologia , Humanos , Mentol/farmacologia , Nicotina , Fumantes , Adulto Jovem
19.
Curr Pharm Biotechnol ; 22(7): 983-994, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32881666

RESUMO

BACKGROUND: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. OBJECTIVE: The effect of combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. METHODS: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. RESULTS: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. Higher activity was correlated to the presence of flavors and nicotine. DISCUSSION: In most cases, the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to the presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. CONCLUSION: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.


Assuntos
Antibacterianos/farmacologia , Sistemas Eletrônicos de Liberação de Nicotina , Aromatizantes/farmacologia , Glicerol/farmacologia , Estudo de Prova de Conceito , Propilenoglicol/farmacologia , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/fisiologia , Testes de Sensibilidade Microbiana/métodos , Nicotina/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
20.
Int J Biol Macromol ; 170: 129-139, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33338530

RESUMO

In this study, the microbiological, physicochemical, and flavor changes of turbot (Scophthalmus maximus) coated with a composite active coating of locust bean gum (LBG) and sodium alginate (SA) supplemented with daphnetin emulsions (0.16, 0.32, 0.64 mg·mL-1) were determined during 18 days of refrigerated storage (4 ± 1 °C). Results showed that LBG-SA coatings containing 0.32 mg·mL-1 daphnetin emulsions could significantly lower the total viable count (TVC), psychrophiles, Pseudomonas spp. and H2S-producing bacteria counts, and inhibit the productions of off-flavor compounds including the total volatile basic nitrogen (TVB-N), trimethylamine (TMA) and ATP-related compounds. 32 volatile compounds were identified by solid phase microextraction combined with gas chromatography-mass spectrometer method (SPME-GC/MS) during refrigerated storage and the treated turbot samples significantly lowered the relative content of fishy flavor compounds. Further, the LBG-SA coatings containing daphnetin could also delay the myofibril degradation of the turbot samples. These results indicated that the LBG-SA coatings with 0.32 mg·mL-1 daphnetin were a potential alternative way to improve the quality of turbot during refrigerated storage.


Assuntos
Alginatos/farmacologia , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Criopreservação , Linguados , Conservação de Alimentos , Conservantes de Alimentos/farmacologia , Galactanos/farmacologia , Mananas/farmacologia , Carne , Gomas Vegetais/farmacologia , Umbeliferonas/farmacologia , Alginatos/administração & dosagem , Animais , Antibacterianos/administração & dosagem , Antioxidantes/administração & dosagem , Carga Bacteriana , Emulsões , Linguados/microbiologia , Aromatizantes/administração & dosagem , Aromatizantes/farmacologia , Microbiologia de Alimentos , Conservantes de Alimentos/administração & dosagem , Galactanos/administração & dosagem , Cromatografia Gasosa-Espectrometria de Massas , Lecitinas/administração & dosagem , Lecitinas/farmacologia , Mananas/administração & dosagem , Carne/microbiologia , Metilaminas/análise , Miofibrilas/efeitos dos fármacos , Nitrogênio/análise , Gomas Vegetais/administração & dosagem , Pseudomonas/efeitos dos fármacos , Umbeliferonas/administração & dosagem , Compostos Orgânicos Voláteis/análise
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